Prioritized imputed sequence variants from multi-population GWAS improve prediction accuracy for sea lice count in Atlantic salmon (Salmo salar)

Abstract

Sea lice infestation is one of the major fish health problems that occurs during the grow-out phase in Atlantic salmon (Salmo salar) aquaculture. In this study, we integrated different genomic approaches, including whole-genome sequencing (WGS), genotype imputation and meta-analysis of genome-wide association studies (GWAS), to identify single-nucleotide polymorphisms (SNPs) associated with sea lice count in Atlantic salmon. Different sets of trait-associated SNPs were prioritized and compared against randomly chosen markers, based on the accuracy of genomic predictions for the trait. Lice count phenotypes and dense genotypes of five breeding populations challenged with sea lice were used. Genotype imputation was applied to increase SNP density of challenged animals to WGS level. The summary statistics from GWAS of each population were then combined in a meta-analysis to increase the sample size and improve the statistical power of associations. Eight different genotyping scenarios were considered for genomic prediction: 70K_array: 70 K standard genotyping panel; 70K_priori: 70 K SNPs with the highest p-values identified in the meta-analysis; 30K_priori: 30 K SNPs with the highest p-values identified in the meta-analysis; WGS: SNPs imputed to whole-genome sequencing level. The remaining four scenarios were the same SNP sets with a linkage disequilibrium (LD) pruning filter: 70K_array_LD; 70K_priori_LD; 30K_priori_LD and WGS_LD. Genomic prediction accuracy was evaluated using a five-fold cross-validation scheme in two different populations which were excluded from the meta-analysis to remove possible validation-reference bias. Results showed significant genetic variation for the number of sea lice in Atlantic salmon across populations, with heritabilities ranging from 0.06 to 0.24. The meta-analysis identified several SNPs associated with sea lice resistance, mainly in Ssa03 and Ssa09 chromosomes. Genomic prediction using the GWAS-based prioritized SNPs showed higher accuracy compared to the standard SNP array in most of scenarios; achieving up to 57% increase in accuracy. Accuracy of prioritized scenarios was higher for the 70K_priori than the 30K_priori. The use of WGS data in genomic prediction presented marginal or negative accuracy gain compared to the standard SNP array. The LD-pruning filter presented no benefits, reducing accuracy in most scenarios. Overall, our study demonstrated the potential of prioritized imputed sequence variants from multi-population GWAS meta-analysis to improve prediction accuracy for sea lice counts in Atlantic salmon. The findings suggest that incorporating WGS data and prioritized SNPs from GWAS meta-analysis can accelerate the genetic progress of selection for polygenic traits in salmon aquaculture.